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81.
Dale DC; Bonilla MA; Davis MW; Nakanishi AM; Hammond WP; Kurtzberg J; Wang W; Jakubowski A; Winton E; Lalezari P 《Blood》1993,81(10):2496-2502
Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony- stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. 相似文献
82.
Blood cells participate in the fibrinolytic response to tissue-type plasminogen activator 总被引:1,自引:0,他引:1
Exercise and venous occlusion stimulate fibrinolysis. In addition to increased concentrations of tissue-type plasminogen activator (tPA) and increased plasmin-mediated fibrinolysis in plasma, these stimuli produce additional cellular-phase activity in blood that is of the same magnitude as the plasma response. To determine whether tPA alone, rather than other consequences of these stimuli, is responsible for the cellular response, the in vitro effects of tPA on whole blood, plasma, and calculated cellular-phase (whole blood minus plasma) activities were determined by solid-phase radiofibrin assay on venous blood from ten normal subjects (seven men, three women). At tPA concentrations encompassing physiological and therapeutic levels (5 to 100 ng/mL; 0.7 to 14 IU/mL), increments in whole blood were consistently in excess of those in companion plasma and represented increased cellular-phase activity equivalent in magnitude to the well-known increase in plasma activity. Fibrinolytic activity produced by 10 to 20 ng tPA/mL (1.4 to 2.8 IU/mL) was consistently detected in whole blood and plasma by 60 minutes, with higher concentrations (100 ng or 14 IU tPA/mL) detectable after a five-minute assay in all subjects. Thus, tPA alone, without invoking fibrinolytic factors extraneous to blood or other effects of exercise or venous occlusion, accounts for both cellular and plasma responses to these stimuli. The considerable cellular response, the mechanism of which remains to be elucidated, may constitute a determinant of individual therapeutic responsiveness to tPA. 相似文献
83.
HK Ulatowska G Streit Olness MW Keebler KE Goins 《International journal of speech-language pathology》2013,15(1):3-14
This investigation explores the discourse devices associated with high-quality personal narratives. The study examined normative characteristics of 11 high-quality personal narratives of a frightening experience identified (from a larger set of 72 narratives) for their effectiveness in engaging the audience. Lay ratings and an ethnographic interview with seven of the excellent storytellers further characterized the stories and validated their selection. Narratives of both African Americans and Caucasians were represented, and were similar in nature. The excellent narratives were longer, conveyed more fearful topics, and were more dramatic than average narratives. Drama was achieved through direct speech, prosodic shifts, voice changes, inclusion of multiple characters, repetition, and syntactic and semantic parallelism. Illustrative narrative excerpts are provided. This study illustrates the potential in pairing holistic and analytical approaches to narrative analysis. 相似文献
84.
Lydian Veldhuis Mirjam K Struijk Willemieke Kroeze Anke Oenema Carry M Renders Anneke MW Bulk-Bunschoten Remy A HiraSing Hein Raat 《BMC public health》2009,9(1):177
Background
The prevalence of overweight and obesity in children has at least doubled in the past 25 years with a major impact on health. In 2005 a prevention protocol was developed applicable within Youth Health Care. This study aims to assess the effects of this protocol on prevalence of overweight and health behaviour among children. 相似文献85.
GL Ray KE Baidoo KJ Wong M Williams K Garmestani MW Brechbiel DE Milenic 《British journal of pharmacology》2009,157(8):1541-1548
Background and purpose:
The studies described here are the first to evaluate the in vitro and in vivo properties of 111In-CHX-A″-panitumumab for radioimmunotherapy (α- and β--emitters) and radioimmunoimaging (single photon emission computed tomography and positron emission tomography).Experimental approach:
Twenty-seven human carcinoma cell lines were analysed for expression of epidermal growth factor receptors by flow cytometry. Panitumumab was conjugated with CHX-A″-DTPA (diethylenetriamine-pentaacetic acid) and radiolabelled with 111In. Immunoreactivity of the CHX-A″-DTPA-panitumumab and 111In-CHX-A″-DTPA-panitumumab was evaluated by radioimmunoassays. Tumour targeting was determined in vivo by direct quantitation of tumour and normal tissues and by γ-scintigraphy.Key results:
For 26 of 27 human tumour cell lines, 95% of the cells expressed epidermal growth factor receptors over a range of intensity. Immunoreactivity of panitumumab was retained after modification with CHX-A″-DTPA. Radiolabelling of the immunoconjugate with 111In was efficient with a specific activity of 19.5 ± 8.9 mCi·mg−1 obtained. Immunoreactivity and specificity of binding of the 111In-panitumumab was shown with A431 cells. Tumour targeting by 111In-panitumumab was demonstrated in athymic mice bearing A431, HT-29, LS-174T, SHAW or SKOV-3 s.c. xenografts with little uptake observed in normal tissues. The 111In-panitumumab was also evaluated in non-tumour-bearing mice. Pharmacokinetic studies compared the plasma retention time of the 111In-panitumumab in both non-tumour-bearing and A431 tumour-bearing mice. Tumour targeting was also visualized by γ-scintigraphy.Conclusions and implications:
Panitumumab can be efficiently radiolabelled with 111In with high labelling yields. Based on the efficiency in tumour targeting and low normal tissue uptake, panitumumab may be an effective targeting component for radioimmunodiagnostic and radioimmunotherapeutic applications. 相似文献86.
Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET) 总被引:1,自引:0,他引:1
Schoenig GP; Osimitz TG; Gabriel KL; Hartnagel R; Gill MW; Goldenthal EI 《Toxicological sciences》1999,47(1):99-109
Chronic toxicity and/or oncogenicity studies were conducted in rats, mice,
and dogs with the insect repellent DEET. DEET was mixed in the diet and
administered to CD rats for two years at concentrations that corresponded
to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400
mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250,
500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at
dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each
group consisted of 60 animals of each sex, and two concurrent independent
control groups, each containing 60 animals/sex were included in each study.
Each group in the dog study consisted of four male and four female dogs and
one control group was included in the study. Treatment-related effects were
observed at the highest dose level in all three studies. For rats, the
effects included decreases in body weight and food consumption and an
increase in serum cholesterol in females only. In mice, the effects
observed were decreases in body weight and food consumption in both sexes.
The effects observed in dogs included increased incidences of emesis and
ptyalism, and levels of transient reduction in hemoglobin and hematocrit,
increased alkaline phosphatase (males only), decreased cholesterol, and
increased potassium. One male dog in the high-dose group also exhibited
ataxia, tremors, abnormal head movements, and/or convulsions on several
occasions during the study. The highest no- observed-effect levels (NO-ELs)
for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day,
respectively. No specific target organ toxicity or oncogenicity was
observed in any of the studies.
相似文献
87.
88.
Ultrasound examination of the hydatic liver 总被引:9,自引:0,他引:9
89.
The multifaceted roles of nitric oxide in cancer 总被引:36,自引:9,他引:36
The roles of nitric oxide (NO) in numerous disease states have generated
considerable discussion over the past several years. NO has been labeled as
the causative agent in different pathophysiological mechanisms, yet appears
to protect against various chemical species such as those generated under
oxidative stress. Similarly, NO appears to exert a dichotomy of effects
within the multistage model of cancer. Chronic inflammation can lead to the
production of chemical intermediates, among them NO, which in turn can
mediate damage to DNA. Yet, NO also appears to be critical for the
tumoricidal activity of the immune system. Furthermore, NO can also have a
multitude of effects on other aspects of tumor biology, including
angiogenesis and metastasis. This report will discuss how the chemistry of
NO may impact the initiation and progression stages of cancer.
相似文献
90.
Expanding the therapeutic repertoire of epidermal growth factor receptor blockade: radiosensitization 下载免费PDF全文
Expression of epidermal growth factor receptor (EGFR) has been associated with radioresistance in cancer. Moreover, tumour cell recovery after irradiation paradoxically occurs, in part, as a result of activation of EGFR signalling by such treatment. A recent article by Huang, Li, Armstrong and Harari provides strong rationale for considering the anti-EGFR agent ZD1839 ('Iressa') as a radiosensitizing strategy. With the use of several in vitro and xenograft models of human squamous cell head and neck carcinoma, ZD1939 was shown to markedly improve radiotherapeutic response, with superior tumour inhibition and delayed tumour regrowth. Mechanisms underlying this effect included anti-proliferative and pro-apoptotic activity, with significant perturbation of tumour angiogenesis. 相似文献